Exploring the Scope for Scale-Up of Organic Chemistry Using a Large Batch Microwave Reactor

Abstract

A new batch microwave reactor has been evaluated in the context of palladium-mediated transformations, condensation reactions, nucleophilic aromatic substitution reactions, and alkylations. Importantly, a linear scaling approach was taken, no changes being made to the protocol when moving from the small, developmental scale to larger scales. In some cases reactions were scaled over 18,000-fold when moving from small (0.1-1 mmol) to large (1-18 mol) runs.

Synthesis of 9-substituted 9-deazaguanine derivatives

“…Several procedures are described for the preparation of the starting material, 6-methyl-4-pyrimidinone derivatives 1, using guanidine or thiourea, ethyl acetoacetate, with or without base, under reflux of ethanol or methanol for several hours. 4,5 Schmink et al 6 described recently a MW assisted synthesis of 6-methylthiouracil (1b) using KOH in ethanol. We tested the reaction for the preparation of 1a-c with and without base, solvent, under conventional heating and also under MW.…”

Development and Design of Reactors in Microwave‐Assisted Chemistry

“…In the last 5-10 years, several papers have been published with examples of scale-up under microwave-assisted conditions [94][95][96][97][98][99][100][101][102][103][104][105]. Of special interest were the topics of reaction optimization, the energy efficiency of microwave heating, and the challenge of scale-up.…”

Reproducibility and Scalability of Microwave-Assisted Reactions

“…One batch provided 250 g of dihydropyridine product in less than 1 h. Leadbeater et al evaluated a new batch reactor, designed by AccelBeam Synthesis, that allows reactions to be performed on scales from 2-12 L (Schmink et al, 2010). A number of reactions have been investigated, including palladium-mediated transformations, condensation reactions, nucleophilic aromatic substitution reactions, and alkylations.…”